Marginal populations are often isolated and under extreme selection pressures resulting in anomalous genetics. Consequently, ecosystems that are geographically and ecologically marginal might have a large share of genetically atypical populations, in need of particular concern in management of these ecosystems. To test this prediction, we analysed genetic data from 29 species inhabiting the low saline Baltic Sea, a geographically and ecologically marginal ecosystem. On average Baltic populations had lost genetic diversity compared to Atlantic populations: a pattern unrelated to dispersal capacity, generation time of species and taxonomic group of organism, but strongly related to type of genetic marker (mitochondrial DNA loci had lost c. 50% diversity, and nuclear loci 10%). Analyses of genetic isolation by geographic distance revealed clinal patterns of differentiation between Baltic and Atlantic regions. For a majority of species, clines were sigmoid with a sharp slope around the Baltic Sea entrance, indicating impeded gene flows between Baltic and Atlantic populations. Some species showed signs of allele frequencies being perturbed at the edge of their distribution inside the Baltic Sea. Despite the short geological history of the Baltic Sea (8000 years), populations inhabiting the Baltic have evolved substantially different from Atlantic populations, probably as a consequence of isolation and bottlenecks, as well as selection on adaptive traits. In addition, the Baltic Sea also acts a refuge for unique evolutionary lineages. This marginal ecosystem is thus vulnerable but also exceedingly valuable, housing unique genes, genotypes and populations that constitute an important genetic resource for management and conservation.