Integrated transcriptomics and metabolomics analyses reveal benzo[a]pyrene enhances the toxicity of mercury to the Manila clam, Ruditapes philippinarum.

Mercury (Hg) and benzo[a]pyrene (BaP) are ubiquitous and persistent pollutants with multiple toxicities in bivalve molluscs. Here, the toxicological responses in the gills of Manila clams, Ruditapes philippinarum, to Hg (10 μg L), BaP (3 μg L), and their mixture were analysed using transcriptomics and metabolomics approaches. Comparisons of the transcriptomes and metabolomes of Hg-and/or BaP-treated clams with control animals revealed the involvement of the detoxification metabolism, immune defence, energy-related pathways, and osmotic regulation in the stress response of R. philippinarum. Exposure to Hg alone primarily enhanced the detoxification and energy metabolic pathways by significantly increasing the expression of genes associated with heat-shock proteins and oxidative phosphorylation. However, co-exposure to Hg and BaP caused greater immunotoxicity and disrupted detoxification metabolism, the TCA cycle, glycolysis, and ATP generation. The expression levels of cytochrome P450 1A1 (CYP1A1), multidrug resistance-associated protein 1 (MRP1), and myosin (MYO), and the activity of electron transport system (ETS) in gills were detected, supporting the underlying toxic mechanisms of Hg and BaP. We suggest that the presence of BaP enhances the toxicity of Hg by 1) hampering the detoxification of Hg, 2) increasing the immunotoxicity of Hg, and 3) constraining energy availability for clams.