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Characterizing the structure and functioning of marine ecosystems requires a deep understanding of the dynamics of its populations and the biotic interactions among them. To this end, we developed a mass-balanced food-web model of a regional sea in the Northeast Atlantic, the Bay of Biscay (BoB), considering one of the most important anthropogenic disturbance in the area, the fishing pressure. The food-web model was performed for the whole BoB region for the first time. The model represents the ecosystems in the early 2000s, encompassing 120433 km2 between 0 and 1000 m depth. The model was composed of 52 functional groups, ranging from primary producers to top predators, and considering both Spanish and French fishing fleets. Input data included biomass obtained locally from bottom trawl and acoustic surveys, data from stock assessment, official fishery statistics, published and unpublished data on stomach content analyses and the use of empirical equations to estimate consumption and production rates. Our results highlight the importance of the pelagic domain, since the main trophic flows are determined by the interaction between phytoplankton, zooplankton and forage fishes. The role of the detritivore pathway was also relevant due to the relatively high abundance of detritivores organisms and the large percentage of primary production flowing to the detritus. Forage fish have resulted to be a key compartment fostering the connectivity between the benthic and pelagic domains. Pelagic sharks, dolphins, anglerfish, large hake and large demersal fishes were identified as potential keystone functional groups in the BoB model. The results also showed an intense exploitation by fisheries in early 2000s. Different strategies between Spanish and French fleets were also found. French fleets were mainly focussed on low trophic level forage fish (e.g., sardine and anchovy) and had larger impacts on higher trophic levels, while Spanish fleets mostly focussed on higher trophic level forage fishes (e.g., mackerel, horse mackerel and blue whiting) but also targeting sardine and anchovy; and displayed lower impacts on higher trophic levels. Overall, our model demonstrates the importance of combining data sources from different countries to regionally address the sought-after implementation of the ecosystem-based management approach. [Display omitted] • We characterize the structure and functioning of the whole Bay of Biscay with a food web model. • The model highlights the dominance of the pelagic domain and the importance of the detritivore pathway. • Forage fish play a key role in fostering the connectivity between the benthic and pelagic domains. • The results show an intense exploitation by fisheries in early 2000s. • The model highlight different strategies between Spanish and French fleets. [ABSTRACT FROM AUTHOR]