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The present study aims to evaluate the effects of copper and silver alone or along with a moderate temperature increase on embryonic development, DNA integrity and target gene expression levels in early life stages of Mytilus galloprovincialis. For this purpose, upon fertilized embryos were exposed to a sub-lethal concentration of Cu (9.54 mu g/L), Ag (2.55 mu g/L) and to the mixture of the two metals (Cu (6.67 mu g/L) + Ag (1.47 mu g/L)) along with a temperature gradient (18, 20 and 22 degrees C). In all experiments, larvae were exposed to stressors for 48 h except for those designed to DNA damage analysis exposed only for 24 h (before shell formation). Our results showed a significant increase in the percentage of malformed D-larvae (p < 0.05) with increasing temperature and exposure to silver and copper alone or in a mixture. Moreover, metal toxicity increased significantly (p < 0.05) with the temperature rise. Genotoxicity was evaluated using classic and modified with Formamidopyrimidine DNA glycosylase (Fpg) Comet assay. Results suggest that co-exposure to metals and temperature significantly increased DNA damage on mussel larvae with a more accentuated oxidative damage. A significant transcription modulation was observed for genes involved in DNA repair and DNA replication (p53, DNA ligase II and topoisomerase II) when larvae are exposed to a single stressor. However, in the case of multiple stresses, caspase involved in the cell apoptosis pathway was overexpressed. Our study suggests that mussel larvae exposed to a moderate increase in temperature may have a compromised ability to defend against genotoxicity. This is particularly relevant in the context of global warming and thermal pollution. (C) 2019 Elsevier B.V. All rights reserved.