Hybrids betweenSchistosoma haematobiumandS. bovisare linked to both human and animal infections, highlighting the complex interspecies interactions that contribute to the spread of schistosomiasis. Additionally,S. boviscan infect multiple ruminant hosts, facilitating cross- species transmission and increasing the risk of zoonotic outbreaks. In this study, we investigated transcriptomic plasticity as a potential mechanism enabling hybrid schistosomes to adapt to alternative definitive hosts. We focused on two contexts: 1) introgressedS. haematobium × S. bovishybrids, which demonstrated higher virulence in sheep compared to parentalS. bovis, and 2)S. bovisinfecting different host species. Our analysis uncovered 366 differentially expressed genes (DEGs), representing 4% of the total protein-coding genes, between introgressed hybrids and parentalS. bovisin sheep. We also identified transcriptomic changes inS. bovisacross different mammalian hosts (hamster and sheep), with around 30% of the total genes differentially expressed, demonstrating thatS. bovisparasites display a high transcriptomic plasticity, allowing them to infect different definitive hosts. Shared enriched biological processes during introgression and host change include nuclear-transcribed mRNA catabolic processes, inner mitochondrial membrane organization, microtubule-based movement, response to endoplasmic reticulum stress, and sensory perception. These findings suggest that transcriptomic plasticity inS. bovisand hybrid worms enhance their ability to adapt and infect diverse host species, potentially increasing their zoonotic potential. This raises concerns for schistosomiasis epidemiology, as this plasticity could expand the parasite’s transmission capacity and complicate control efforts.