Transcriptomic reprogramming underlies perfluorobutanoic acid (PFBA)-induced hormesis in the fall armyworm, Spodoptera frugiperda

Short-chain perfluoroalkyl substances (PFAS), such as perfluorobutanoic acid (PFBA), are increasingly detected in agricultural soils, irrigation water, and crop tissues, yet their biological effects at low, environmentally relevant concentrations remain poorly understood. Here, we investigated the dose-dependent effects of PFBA on growth, feeding, development, and gene expression in the fall armyworm (Spodoptera frugiperda). Across a broad concentration range, PFBA elicited a biphasic response characterized by low-dose stimulation and high-dose inhibition of larval growth. PFBA exposure across low concentrations (0.001-10 µg/g) enhanced early feeding and accelerated growth, leading to earlier attainment of developmental milestones, including reduced time to pupation and adult emergence. In contrast, higher concentrations suppressed growth. Transcriptomic analyses revealed that these contrasting phenotypes were underpinned by distinct, dose- and time-dependent transcriptional programs. Low-dose exposure induced a coordinated progression from early activation of structural and contractile pathways to enrichment of developmental and morphogenetic processes, consistent with accelerated maturation. In contrast, high-dose exposure triggered stress-associated transcriptional states, including activation of detoxification, oxidative stress, and neuronal signaling pathways, alongside suppression of endocrine and metabolic regulators. Together, these findings demonstrate that PFBA-induced hormesis reflects structured reprogramming of growth and developmental pathways rather than simple metabolic stimulation. By linking dose-resolved phenotypic responses with global transcriptomic organization, this study provides mechanistic insight into how short-chain PFAS can act as both modulators of biological performance and toxic stressors. Given the increasing prevalence of PFBA in agricultural systems, these results highlight the importance of incorporating non-monotonic dose-response relationships into ecological risk assessment and evaluating how PFAS exposure may influence pest dynamics in agroecosystems.