The present study aimed at assessing the singular and combined effects of water copper and polyvinyl chloride microplastic (MPVC) on intestinal copper accumulation, histopathological damage, and stress‐/immune‐related genes' expression in common carp, Cyprinus carpio. Four groups of fish were maintained in triplicate: control (kept in clean water), Cu (exposed to 0.25 mg/L of copper), MPVC (exposed to 0.5 mg/L of MPVC), and Cu‐MPVC (exposed to 0.25 mg/L of copper + 0.5 mg/L of MPVC). After 14‐day exposure, the fish of Cu and Cu‐MPVC treatments exhibited significantly higher intestinal copper contents, compared to the fish of control and MPVC treatments. In this regard, the Cu‐MPVC fish had significantly higher copper content than the Cu fish. Exposure to copper and/or MPVC significantly upregulated the intestinal heat shock protein 70 (hsp70), cytochrome P450 family 1 subfamily A member 1 (cyp1a1), lysozyme (lys), defensin (def), mucin 2 (muc2), and mucin 5 (muc5) expression. The highest expression of hsp70, cyp1a1, lys, and def was related to Cu‐MPVC treatment; whereas, the highest expression of muc2 and muc5 was observed in Cu and MPVC treatments. Exposure to copper and/or MPVC induced intestinal damage, which Cu‐MPVC fish exhibited the highest severity. The present study revealed that exposure to copper and/or MPVC causes intestinal histopathological damage and upregulation in stress‐ and immune‐related genes' expression. The most serious effects were observed in Cu‐MPVC treatment that might be due to additive effects of copper and MPVC and/or higher copper accumulation in this treatment.

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