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Once in the marine environment, fishing nets and cables undergo weathering, breaking down into micro and nano-size particles and leaching plastic additives, which negatively affect marine biota. This study aims to unravel the ecotoxicological impact of different concentrations of leachate obtained from abandoned or lost fishing nets and cables in the mussel Mytilus galloprovincialis under long-term exposure (28 days). Biochemical biomarkers linked to antioxidant defense system, xenobiotic biotransformation, oxidative damage, genotoxicity, and neurotoxicity were evaluated in different mussel tissues. The chemical nature of the fishing nets and cables and the chemical composition of the leachate were assessed and metals, plasticizers, UV stabilizers, flame retardants, antioxidants, dyes, flavoring agents, preservatives, intermediates and photo initiators were detected. The leachate severely affected the antioxidant and biotransformation systems in mussels’ tissues. Following exposure to 1 mg·L-1 of leachate, mussels' defense system was enhanced to prevent oxidative damage. In contrast, in mussels exposed to 10 and 100 mg·L-1 of leachate, defenses failed to overcome pro-oxidant molecules, resulting in genotoxicity and oxidative damage. Principal component analysis (PCA) and Weight of Evidence (WOE) evaluation confirmed that mussels were significantly affected by the leachate being the hazard of the leachate concentrations of 10 mg·L-1 ranked as major, while 1 and 100 mg·L-1 was moderate. These results highlighted that the leachate from fishing nets and cables can be a threat to the heath of the mussel M. galloprovincialis.