PFOS is a toxic, persistent environmental pollutant which is widespread worldwide. PFOS contamination has entered the food chain and is interfering with normal development in man and is neurotoxic, hepatotoxic and tumorigenic. The earthworm, Eisenia fetida is one of the organisms which can help to diagnose soil health and contamination at lower levels in the food chain. Studying the chronic effects of sub-lethal PFOS exposure in such an organism is therefore appropriate. As PFOS bioaccumulates and is not easily biodegraded, it is biomagnified up the food chain. Gene expression studies will give us information to develop biomarkers for early diagnosis of soil contamination, well before this contaminant passes up the food chain. We have carried out mRNA sequencing of control and chronically PFOS exposed E. fetida and reconstructed the transcripts in silico and identified the differentially expressed genes. Our findings suggest that PFOS up/down regulates neurodegenerative-related human homologues and can cause neuronal damage in E. fetida. This information will help to understand the links between neurodegenerative disorders and environmental pollutants such as PFOS. Furthermore, these up/down regulated genes can be used as biomarkers to detect a sub-lethal presence of PFOS in soil. Neuronal calcium sensor-2, nucleoside diphosphate kinase, polyadenylate-binding protein-1 and mitochondrial Pyruvate dehydrogenase protein-X component, could be potential biomarkers for sub lethal concentrations of PFOS.