Creating New Antifoulants Using the Tools and Tactics of Medicinal Chemistry.

ConspectusThe unwanted accumulation of marine micro- and macroorganisms such as algae and barnacles on submerged man-made structures and vessel hulls is a major challenge for any marine operation. Known as biofouling, this problem leads to reduced hydrodynamic efficiency, significantly increased fuel usage, microbially induced corrosion, and, if not managed appropriately, eventual loss of both performance and structural integrity. Ship hull biofouling in the international maritime transport network conservatively accounts for 0.6% of global carbon emissions, highlighting the global scale and the importance of this problem. Improved antifouling strategies to limit surface colonization are paramount for essential activities such as shipping, aquaculture, desalination, and the marine renewable energy sector, representing both a multibillion dollar cost and a substantial practical challenge. From an ecological perspective, biofouling is a primary contributor to the global spread of invasive marine species, which has extensive implications for the marine environment.Historically, heavy metal-based toxic biocides have been used to control biofouling. However, their unwanted collateral ecological damage on nontarget species and bioaccumulation has led to recent global bans. With expanding human activities within aquaculture and offshore energy, it is both urgent and apparent that environmentally friendly surface protection remains key for maintaining the function of both moving and stationary marine structures. Biofouling communities are typically a highly complex network of both micro- and macroorganisms, representing a broad section of life from bacteria to macrophytes and animals. Given this diversity, it is unrealistic to expect that a single antifouling "silver bullet" will prevent colonization with the exception of generally toxic biocides. For that reason, modern and future antifouling solutions are anticipated to rely on novel coating technologies and "combination therapies" where mixtures of narrow-spectrum bioactive components are used to provide coverage across fouling species. In contrast to the existing cohort of outdated, toxic antifouling strategies, such as copper- and tributyltin-releasing paints, modern drug discovery techniques are increasingly being employed for the rational design of effective yet safe alternatives. The challenge for a medicinal chemistry approach is to effectively account for the large taxonomic diversity among fouling organisms combined with a lack of well-defined conserved molecular targets within most taxa.The current Account summarizes our work employing the tools of modern medicinal chemistry to discover, modify, and develop optimized and scalable antifouling solutions based on naturally occurring antifouling and repelling compounds from both marine and terrestrial sources. Inspiration for rational design comes from targeted studies on allelopathic natural products, natural repelling peptides, and secondary metabolites from sessile marine organisms with clean exteriors, which has yielded several efficient and promising antifouling leads.

A supergene in seaweed flies modulates male traits and female perception.

Supergenes, tightly linked sets of alleles, offer some of the most spectacular examples of polymorphism persisting under long-term balancing selection. However, we still do not understand their evolution and persistence, especially in the face of accumulation of deleterious elements. Here, we show that an overdominant supergene in seaweed flies, Coelopa frigida, modulates male traits, potentially facilitating disassortative mating and promoting intraspecific polymorphism. Across two continents, the Cf-Inv(1) supergene strongly affected the composition of male cuticular hydrocarbons (CHCs) but only weakly affected CHC composition in females. Using gas chromatography-electroantennographic detection, we show that females can sense male CHCs and that there may be differential perception between genotypes. Combining our phenotypic results with RNA-seq data, we show that candidate genes for CHC biosynthesis primarily show differential expression for Cf-Inv(1) in males but not females. Conversely, candidate genes for odorant detection were differentially expressed in both sexes but showed high levels of divergence between supergene haplotypes. We suggest that the reduced recombination between supergene haplotypes may have led to rapid divergence in mate preferences as well as increasing linkage between male traits, and overdominant loci. Together this probably helped to maintain the polymorphism despite deleterious effects in homozygotes.

Evaluation of natural resveratrol multimers as marine antifoulants.

In the current study we investigate the antifouling potential of three polyphenolic resveratrol multimers (-)-hopeaphenol, vaticanol B and vatalbinoside A, isolated from two species of Anisoptera found in the Papua New Guinean rainforest. The compounds were evaluated against the growth and settlement of eight marine microfoulers and against the settlement and metamorphosis of Amphibalanus improvisus barnacle cyprids. The two isomeric compounds (-)-hopeaphenol and vaticanol B displayed a high inhibitory potential against the cyprid larvae metamorphosis at 2.8 and 1.1 µM. (-)-Hopeaphenol was also shown to be a strong inhibitor of both microalgal and bacterial adhesion at submicromolar concentrations with low toxicity. Resveratrol displayed a lower antifouling activity compared to the multimers and had higher off target toxicity against MCR-5 fibroblasts. This study illustrates the potential of natural products as a valuable source for the discovery of novel antifouling leads with low toxicity.

Ocean acidification reduces thallus strength in a non-calcifying foundation seaweed.

Climate change is causing unprecedented changes in terrestrial and aquatic ecosystems through the emission of greenhouse gases, including carbon dioxide (CO2). Approximately 30% of CO2 is taken up by the ocean ('ocean acidification', OA)1, which has profound effects on foundation seaweed species. Negative physical effects on calcifying algae are clear2, but studies on habitat-forming fleshy seaweeds have mainly focused on growth and less on thallus strength3,4. We exposed the habitat-forming brown seaweed Fucus vesiculosus to OA corresponding to projected climate change effects for the year 2100, and observed reduced apical thallus strength and greater loss of exposed individuals in the field. The tissue contained less calcium and magnesium, both of which are important for creating structural alginate matrices. Scanning electron microscopy (SEM) revealed tissue voids in the OA samples that were not present in seaweeds grown under ambient pCO2. We conclude that under OA, weakened F. vesiculosus will be at a significantly higher risk of physical damage and detachment.

Ten years of marine evolutionary biology-Challenges and achievements of a multidisciplinary research initiative.

The Centre for Marine Evolutionary Biology (CeMEB) at the University of Gothenburg, Sweden, was established in 2008 through a 10-year research grant of 8.7 m€ to a team of senior researchers. Today, CeMEB members have contributed >500 scientific publications, 30 PhD theses and have organised 75 meetings and courses, including 18 three-day meetings and four conferences. What are the footprints of CeMEB, and how will the centre continue to play a national and international role as an important node of marine evolutionary research? In this perspective article, we first look back over the 10 years of CeMEB activities and briefly survey some of the many achievements of CeMEB. We furthermore compare the initial goals, as formulated in the grant application, with what has been achieved, and discuss challenges and milestones along the way. Finally, we bring forward some general lessons that can be learnt from a research funding of this type, and we also look ahead, discussing how CeMEB's achievements and lessons can be used as a springboard to the future of marine evolutionary biology.

Mild blanching prior to pH-shift processing of Saccharina latissima retains protein extraction yields and amino acid levels of extracts while minimizing iodine content.

The seaweed Saccharina latissima is often blanched to lower iodine levels, however, it is not known how blanching affects protein extraction. We assessed the effect of blanching or soaking (80/45/12 °C, 2 min) on protein yield and protein extract characteristics after pH-shift processing of S. latissima. Average protein yields and extract amino acid levels ranked treatments as follows: blanching-45 °C âˆ¼ control > soaking âˆ¼ blanching-80 °C. Although blanching-45 °C decreased protein solubilization yield at pH 12, it increased isoelectric protein precipitation yield at pH 2 (p < 0.05). The former could be explained by a higher ratio of large peptides/proteins in the blanched biomass as shown by HP-SEC, whereas the latter by blanching-induced lowering of ionic strength, as verified by a dialysis model. Moreover, blanching-45 °C yielded a protein extract with 49 % less iodine compared with the control extract. We recommend blanching-45 °C since it is effective at removing iodine and does not compromise total protein extraction yield.

Salinity and host drive Ulva-associated bacterial communities across the Atlantic-Baltic Sea gradient.

The green seaweed Ulva is a model system to study seaweed-bacteria interactions, but the impact of environmental drivers on the dynamics of these interactions is little understood. In this study, we investigated the stability and variability of the seaweed-associated bacteria across the Atlantic-Baltic Sea salinity gradient. We characterized the bacterial communities of 15 Ulva sensu lato species along 2,000 km of coastline in a total of 481 samples. Our results demonstrate that the Ulva-associated bacterial composition was strongly structured by both salinity and host species (together explaining between 34% and 91% of the variation in the abundance of the different bacterial genera). The largest shift in the bacterial consortia coincided with the horohalinicum (5-8 PSU, known as the transition zone from freshwater to marine conditions). Low-salinity communities especially contained high relative abundances of Luteolibacter, Cyanobium, Pirellula, Lacihabitans and an uncultured Spirosomaceae, whereas high-salinity communities were predominantly enriched in Litorimonas, Leucothrix, Sulfurovum, Algibacter and Dokdonia. We identified a small taxonomic core community (consisting of Paracoccus, Sulfitobacter and an uncultured Rhodobacteraceae), which together contributed to 14% of the reads per sample, on average. Additional core taxa followed a gradient model, as more core taxa were shared between neighbouring salinity ranges than between ranges at opposite ends of the Atlantic-Baltic Sea gradient. Our results contradict earlier statements that Ulva-associated bacterial communities are taxonomically highly variable across individuals and largely stochastically defined. Characteristic bacterial communities associated with distinct salinity regions may therefore facilitate the host's adaptation across the environmental gradient.

Assessing the potential for sea-based macroalgae cultivation and its application for nutrient removal in the Baltic Sea.

Marine eutrophication is a pervasive and growing threat to global sustainability. Macroalgal cultivation is a promising circular economy solution to achieve nutrient reduction and food security. However, the location of production hotspots is not well known. In this paper the production potential of macroalgae of high commercial value was predicted across the Baltic Sea region. In addition, the nutrient limitation within and adjacent to macroalgal farms was investigated to suggest optimal site-specific configuration of farms. The production potential of Saccharina latissima was largely driven by salinity and the highest production yields are expected in the westernmost Baltic Sea areas where salinity is >23. The direct and interactive effects of light availability, temperature, salinity and nutrient concentrations regulated the predicted changes in the production of Ulva intestinalis and Fucus vesiculosus. The western and southern Baltic Sea exhibited the highest farming potential for these species, with promising areas also in the eastern Baltic Sea. Macroalgal farming did not induce significant nutrient limitation. The expected spatial propagation of nutrient limitation caused by macroalgal farming was less than 100-250 m. Higher propagation distances were found in areas of low nutrient and low water exchange (e.g. offshore areas in the Baltic Proper) and smaller distances in areas of high nutrient and high water exchange (e.g. western Baltic Sea and Gulf of Riga). The generated maps provide the most sought-after input to support blue growth initiatives that foster the sustainable development of macroalgal cultivation and reduction of in situ nutrient loads in the Baltic Sea.

Evaluation of early feed access and algal extract on growth performance, organ development, gut microbiota and vaccine-induced antibody responses in broiler chickens.

Hatching concepts such as on-farm hatching provide an opportunity to supply newly hatched chickens with optimal nutrition that support growth and development of a healthy gut. Brown algae contain bioactive compounds, especially laminarin and fucoidan that may improve intestinal health and immune responses. This study aimed to examine the effects of early access to feed and water posthatch and feed supplementation with algal extract rich in laminarin from Laminaria digitata, on growth performance, organ and microbiota development and antibody production. A total of 432 Ross 308 chicks were allotted to 36 rearing pens in a 2 × 3 factorial design with two hatching treatments and three dietary treatments. During chick placement, half of the pens were directly provided access to feed and water (Early) while half of the pens were deprived of feed and water for 38 h (Late). The chicks were fed three different starter diets until day 6; a wheat-soybean meal-based control diet, a diet with low inclusion of algal extract (0.057%) and a diet with high inclusion of algal extract (0.114%). Feed intake and BW were registered on pen basis at placement, days 1, 6, 12, 19, 26, 33 and 40. To induce antibody responses, all chicks were vaccinated against avian pneumovirus on day 10. Three chicks per pen were selected as focal animals and used for blood sampling on days 10 and 39. On days 6, 19, and 40, two birds per pen were killed and used for organ measurement and caecal digesta sampling for gut microbiota analysis using the Illumina Miseq PE 250 sequencing platform. Results showed that algal extract did not influence gut microbiota, gut development or vaccine-induced antibody responses. However, during the first 38 h, early-fed chicks consumed on average 19.6 g of feed and gained 27% in BW, while late-fed chicks lost 9.1% in BW which lowered BW and feed intake throughout the study (P < 0.05). Late chicks also had longer relative intestine, higher relative (g/kg BW) weight of gizzard and proventriculus but lower relative bursa weight on day 6 (P < 0.05). No effects of hatching treatment on microbiota or antibody response were detected. The microbiota was affected by age, where alpha diversity increased with age. In conclusion, this study showed that early access to feed but not algal extract improved the growth performance throughout the 40-day growing period, and stimulated early bursa development.

Towards eco-friendly marine antifouling biocides - Nature inspired tetrasubstituted 2,5-diketopiperazines.

Marine biofouling plagues all maritime industries at vast economic and environmental cost. Previous and most current methods to control biofouling have employed highly persistent toxins and heavy metals, including tin, copper, and zinc. These toxic methods are resulting in unacceptable environmental harm and are coming under immense regulatory pressure. Eco-friendly alternatives are urgently required to effectively mitigate the negative consequence of biofouling without causing collateral harm. Amphiphilic micropeptides have recently been shown to exhibit excellent broad-spectrum antifouling activity, with a non-toxic mode of action and innate biodegradability. The present work focused on incorporating the pharmacophore derived from amphiphilic micropeptides into a 2,5-diketopiperazine (DKP) scaffold. This privileged structure is present in a vast number of natural products, including marine natural product antifoulants, and provides advantages of synthetic accessibility and adaptability. A novel route to symmetrical tetrasubstituted DKPs was developed and a library of amphiphilic 2,5-DKPs were subsequently synthesised. These biodegradable compounds were demonstrated to be potent marine antifoulants displaying broad-spectrum activity in the low micromolar range against a range of common marine fouling organisms. The outcome of planned coating and field trials will dictate the future development of the lead compounds.

A large chromosomal inversion shapes gene expression in seaweed flies (Coelopa frigida).

Inversions often underlie complex adaptive traits, but the genic targets inside them are largely unknown. Gene expression profiling provides a powerful way to link inversions with their phenotypic consequences. We examined the effects of the Cf-Inv(1) inversion in the seaweed fly Coelopa frigida on gene expression variation across sexes and life stages. Our analyses revealed that Cf-Inv(1) shapes global expression patterns, most likely via linked variation, but the extent of this effect is variable, with much stronger effects in adults than larvae. Furthermore, within adults, both common as well as sex-specific patterns were found. The vast majority of these differentially expressed genes mapped to Cf-Inv(1). However, genes that were differentially expressed in a single context (i.e., in males, females, or larvae) were more likely to be located outside of Cf-Inv(1). By combining our findings with genomic scans for environmentally associated SNPs, we were able to pinpoint candidate variants in the inversion that may underlie mechanistic pathways that determine phenotypes. Together the results of this study, combined with previous findings, support the notion that the polymorphic Cf-Inv(1) inversion in this species is a major factor shaping both coding and regulatory variation resulting in highly complex adaptive effects.

Structure-Activity Relationship Probing of the Natural Marine Antifoulant Barettin.

The sponge derived 2,5-diketopiperazine metabolite barettin is a potent antifouling compound effective against the settlement and metamorphosis of barnacles. Simplified derivatives of barettin have previously been shown to display similar inhibitory properties. The synthetic derivative benzo[g]dipodazine has been reported to display significantly improved antifouling properties in comparison with the native barettin with inhibitory activities as low a 0.034 µM reported against barnacle cyprid settlement. In the current study we report the antifouling activity of 29 synthetic analogs designed and inspired by the potent antifouling effect seen for benzo[g]dipodazine. The library contains mainly not only dipodazine derivatives but also disubstituted diketopiperazines and compounds incorporating alternative heterocyclic cores such as hydantoin, creatinine, and rhodanine. Several of the prepared compounds inhibit the settlement of Amphibalanus improvisus cyprids at low micromolar concentrations, in parity with the natural barettin. While several highly active compounds were prepared by incorporating the benzo[g]indole as hydrophobic substituent, the remarkable antifouling effect reported for benzo[g]dipodazine was not observed when evaluated in our study.

In vitro digestibility and Caco-2 cell bioavailability of sea lettuce (Ulva fenestrata) proteins extracted using pH-shift processing.

Seaweed is a promising sustainable source of vegan protein as its farming does not require arable land, pesticides/insecticides, nor freshwater supply. However, to be explored as a novel protein source the content and nutritional quality of protein in seaweed need to be improved. We assessed the influence of pH-shift processing on protein degree of hydrolysis (%DH), protein/peptide size distribution, accessibility, and cell bioavailability of Ulva fenestrata proteins after in vitro gastrointestinal digestion. pH-shift processing of Ulva, which concentrated its proteins 3.5-times, significantly improved the %DH from 27.7±2.6% to 35.7±2.1% and the amino acid accessibility from 56.9±4.1% to 72.7±0.6%. Due to the higher amino acid accessibility, the amount of most amino acids transported across the cell monolayers was higher in the protein extracts. Regarding bioavailability, both Ulva and protein extracts were as bioavailable as casein. The protein/peptide molecular size distribution after digestion did not disclose a clear association with bioavailability.

Ocean acidification decreases grazing pressure but alters morphological structure in a dominant coastal seaweed.

Ocean acidification driven by anthropogenic climate change is causing a global decrease in pH, which is projected to be 0.4 units lower in coastal shallow waters by the year 2100. Previous studies have shown that seaweeds grown under such conditions may alter their growth and photosynthetic capacity. It is not clear how such alterations might impact interactions between seaweed and herbivores, e.g. through changes in feeding rates, nutritional value, or defense levels. Changes in seaweeds are particularly important for coastal food webs, as they are key primary producers and often habitat-forming species. We cultured the habitat-forming brown seaweed Fucus vesiculosus for 30 days in projected future pCO2 (1100 µatm) with genetically identical controls in ambient pCO2 (400 µatm). Thereafter the macroalgae were exposed to grazing by Littorina littorea, acclimated to the relevant pCO2-treatment. We found increased growth (measured as surface area increase), decreased tissue strength in a tensile strength test, and decreased chemical defense (phlorotannins) levels in seaweeds exposed to high pCO2-levels. The herbivores exposed to elevated pCO2-levels showed improved condition index, decreased consumption, but no significant change in feeding preference. Fucoid seaweeds such as F. vesiculosus play important ecological roles in coastal habitats and are often foundation species, with a key role for ecosystem structure and function. The change in surface area and associated decrease in breaking force, as demonstrated by our results, indicate that F. vesiculosus grown under elevated levels of pCO2 may acquire an altered morphology and reduced tissue strength. This, together with increased wave energy in coastal ecosystems due to climate change, could have detrimental effects by reducing both habitat and food availability for herbivores.

Phidianidine A and Synthetic Analogues as Naturally Inspired Marine Antifoulants.

Stationary and slow-moving marine organisms regularly employ a natural product chemical defense to prevent being colonized by marine micro- and macroorganisms. While these natural antifoulants can be structurally diverse, they often display highly conserved chemistries and physicochemical properties, suggesting a natural marine antifouling pharmacophore. In our current report, we investigate the marine natural product phidianidine A, which displays several chemical properties found in highly potent marine antifoulants. Phidianidine A and synthetic analogues were screened against the settlement and metamorphosis of Amphibalanus improvisus cyprids, and several of the compounds displayed inhibitory activities at low micromolar concentrations with IC50 values down to 0.7 µg/mL observed. The settlement study highlights that phidianidine A is a potent natural antifoulant and that the scaffold can be tuned to generate simpler and improved synthetic analogues. The bioactivity is closely linked to the size of the compound and to its basicity. The study also illustrates that active analogues can be prepared in the absence of the natural constrained 1,2,4-oxadiazole ring. A synthetic lead analogue of phidianidine A was incorporated in a coating and included in antifouling field trials, where it was shown that the coating induced potent inhibition of marine bacteria and microalgae settlement.

Ulvan dialdehyde-gelatin hydrogels for removal of heavy metals and methylene blue from aqueous solution.

Hydrogels based on the polysaccharide ulvan from the green macroalgae Ulva fenestrata were synthesized and evaluated as an adsorbent for heavy metals ions and methylene blue. Ulvan was extracted from Ulva fenestrata using diluted hydrochloric acid and recovered by precipitation with EtOH. The extracted ulvan was converted into ulvan dialdehyde via periodate-oxidation and subsequently combined with gelatin yielding hydrogels. The hydrogels showed good water-uptake capacity with a maximum swelling degree of 2400 % in water and 900 % in PBS buffer. Adsorption tests of methylene blue showed a maximum adsorption capacity of 465 mg/g. The adsorption data of methylene blue followed the pseudo-second order kinetics and agreed with the Langmuir adsorption isotherm. The maximum adsorption capacity of heavy metal ions was 14 mg/g for Cu2+, 7 mg/g for Co2+and 6 mg/g for Ni2+and Zn2+ indicating that the hydrogels have a stronger affinity for Cu2+ than for Co2+, Ni2+, and Zn2+.

Environmental impact of kelp (Saccharina latissima) aquaculture.

The aim of the study was to assess the effect of seaweed cultivation on the coastal environment. We analysed a multitude of environmental parameters using an asymmetrical before after control impact (BACI) design, comparing the seaweed farm (impact) with multiple unaffected locations (controls). The seaweed farm had a significant positive effect on benthic infauna (p<0.05) and was found to attract 17 mobile faunal and 7 other seaweed species, indicating that the farmed crop may provide habitat to mobile faunal species. A light attenuation of approximately 40% at 5m depth was noted at the peak of the seaweed biomass just before harvest. No changes were observed in benthic oxygen flux, dissolved nutrient concentrations, and benthic mobile fauna between farm and control sites. These results show that seaweed aquaculture has limited environmental effects, especially compared to other forms of aquaculture such as fish and bivalve farming.

Socioeconomic prospects of a seaweed bioeconomy in Sweden.

Seaweed cultivation is a large industry worldwide, but production in Europe is small compared to production in Asian countries. In the EU, the motivations for seaweed farming may be seen from two perspectives; one being economic growth through biomass production and the other being the provisioning of ecosystem services such as mitigating eutrophication. In this paper, we assess the economic potential of large-scale cultivation of kelp, Saccharina latissima, along the Swedish west coast, including the value of externalities. The findings suggest that seaweed farming has the potential of becoming a profitable industry in Sweden. Furthermore, large-scale seaweed farming can sequester a significant share of annual anthropogenic nitrogen and phosphorus inflows to the basins of the Swedish west coast (8% of N and 60% of P). Concerning the valuation of externalities, positive values generated from sequestration of nitrogen and phosphorus are potentially counteracted by negative values from interference with recreational values. Despite the large N and P uptake, the socioeconomic value of this sequestration is only a minor share of the potential financial value from biomass production. This suggests that e.g. payment schemes for nutrient uptake based on the socioeconomic values generated is not likely to be a tipping point for the industry. Additionally, seaweed cultivation is not a cost-efficient measure in itself to remove nutrients. Policy should thus be oriented towards industry development, as the market potential of the biomass will be the driver that may unlock these bioremediation opportunities.

Genetic divergence and phenotypic plasticity contribute to variation in cuticular hydrocarbons in the seaweed fly Coelopa frigida.

Cuticular hydrocarbons (CHCs) form the boundary between insects and their environments and often act as essential cues for species, mate, and kin recognition. This complex polygenic trait can be highly variable both among and within species, but the causes of this variation, especially the genetic basis, are largely unknown. In this study, we investigated phenotypic and genetic variation of CHCs in the seaweed fly, Coelopa frigida, and found that composition was affected by both genetic (sex and population) and environmental (larval diet) factors. We subsequently conducted behavioral trials that show CHCs are likely used as a sexual signal. We identified general shifts in CHC chemistry as well as individual compounds and found that the methylated compounds, mean chain length, proportion of alkenes, and normalized total CHCs differed between sexes and populations. We combined these data with whole genome resequencing data to examine the genetic underpinnings of these differences. We identified 11 genes related to CHC synthesis and found population-level outlier SNPs in 5 that are concordant with phenotypic differences. Together these results reveal that the CHC composition of C. frigida is dynamic, strongly affected by the larval environment, and likely under natural and sexual selection.

Geographic variation in fitness-related traits of the bladderwrack Fucus vesiculosus along the Baltic Sea-North Sea salinity gradient.

In the course of the ongoing global intensification and diversification of human pressures, the study of variation patterns of biological traits along environmental gradients can provide relevant information on the performance of species under shifting conditions. The pronounced salinity gradient, co-occurrence of multiple stressors, and accelerated rates of change make the Baltic Sea and its transition to North Sea a suitable region for this type of study. Focusing on the bladderwrack Fucus vesiculosus, one of the main foundation species on hard-bottoms of the Baltic Sea, we analyzed the phenotypic variation among populations occurring along 2,000 km of coasts subjected to salinities from 4 to >30 and a variety of other stressors. Morphological and biochemical traits, including palatability for grazers, were recorded at 20 stations along the Baltic Sea and four stations in the North Sea. We evaluated in a common modeling framework the relative contribution of multiple environmental drivers to the observed trait patterns. Salinity was the main and, in some cases, the only environmental driver of the geographic trait variation in F. vesiculosus. The decrease in salinity from North Sea to Baltic Sea stations was accompanied by a decline in thallus size, photosynthetic pigments, and energy storage compounds, and affected the interaction of the alga with herbivores and epibiota. For some traits, drivers that vary locally such as wave exposure, light availability or nutrient enrichment were also important. The strong genetic population structure in this macroalgae might play a role in the generation and maintenance of phenotypic patterns across geographic scales. In light of our results, the desalination process projected for the Baltic Sea could have detrimental impacts on F. vesiculosus in areas close to its tolerance limit, affecting ecosystem functions such as habitat formation, primary production, and food supply.