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

Abstract Mercury (Hg2+) 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 Hg2+ (10 μg L−1), BaP (3 μg L−1), and their mixture were analysed using transcriptomics and metabolomics approaches. Comparisons of the transcriptomes and metabolomes of Hg2+-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 Hg2+ 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 Hg2+ 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 Hg2+ and BaP. We suggest that the presence of BaP enhances the toxicity of Hg2+ by 1) hampering the detoxification of Hg2+, 2) increasing the immunotoxicity of Hg2+, and 3) constraining energy availability for clams.