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With the wide application of plastics in daily life, nanoplastics (NPs) are ubiquitous in freshwater environments. However, to date, few studies have focused on the mechanism underlying the toxicity of NPs, and the differences between this mechanism and that governing the toxicity of MPs have also not been thoroughly characterized. In this study, the genotoxicity, intestinal damage, and intestinal flora in Corbicula fluminea exposed to micro/nanoplastics were investigated through RNA sequencing, histopathology, and 16S rRNA sequencing, respectively. Significant differences in differentially expressed genes (DEGs) were observed between MP and NP exposure groups. It was observed that NPs preferentially elicited the process related to cellular components and triggered the apoptosis through the mitochondrial pathway in various tissues, especially in indirectly contacted tissues, while MPs induced the innate immune response and activated the complement and coagulation cascades (complement system) pathway. Both MPs and NPs can induce an inflammatory response and cause epithelial damage in the intestines, and they can notably change the gut microbial community structure. However, the abundance of pathogenic bacteria (e.g., Mycoplasma) was observed to increase only in the MP-treated group, which exacerbated intestinal damage. Unlike MPs, the effect of NPs on the intestinal microflora was highly limited, while NPs elicited more severe damage to the intestinal mucosal barrier. The results of this study may help to elucidate the toxicity mechanisms governing the responses of bivalves to MPs and NPs and to evaluate the detriment of MPs and NPs to the benthic ecosystem.

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