From Adaptation to Collapse: Immune Remodeling, Mitochondrial Dysfunction, and Cell Death Induced by Polystyrene...

Nanoplastic (NP) pollution threatens aquatic ecosystems, but concentration‑dependent molecular effects remain unclear. Using integrative transcriptomics and metabolomics, we exposed Procambarus clarkii to 200 nm polystyrene nanoplastics (0, 0.5, 1, 2 mg/L) for 28 days. Hepatopancreas analyses revealed a progressive shift from adaptive regulation at low doses to systemic dysfunction at high doses. At low concentrations, PS-NPs induced mild immune activation and ECM remodeling (upregulation of MUC17, ITGB1, CLEC17A). Medium-dose exposure triggered extensive transcriptomic and metabolic reprogramming, including DNA replication/repair activation (H2AX, MCM, PCNA), amino acid depletion, pro-inflammatory lipid accumulation, and elevated RIPK3 expression, indicative of necroptosis. High concentrations caused severe ECM disruption, immune dysregulation, DNA damage, and cell cycle alterations. Key genes (HSP90, CYCA, H2AX) and metabolites (vaccenic acid, L-isoleucine, 1-arachidonoylglycerol) were identified as potential biomarkers of PS-NP-induced stress. Overall, our findings revealed a concentration-dependent toxicological cascade and demonstrated the potential of crayfish as sentinel organisms for evaluating freshwater NP pollution. These results provided a molecular basis for environmental risk assessment and underscore the need to monitor NPs in freshwater ecosystems.