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S.japonicum has a wide range of hosts with different susceptibilities.However,the interplay between parasites and their hosts is complicated and requires further clarification.Epidemiological surveys have revealed that domestic animals play important roles in schistosomiasis transmission in endemic areas in China.Water buffalo and goats are natural hosts for S.japonicum in endemic areas of China.The susceptibility of these two hosts to schistosome infection is different,as water buffalo are less conducive to S.japonicum growth and development.Our study aimed to elucidate the differences between schistosomes from a less:susceptible host (water buffalo) and a susceptible host (goat) at the phenotype and gene expression levels.The worm recovery rate was lower and the length and width of worms from Water buffalo weresmaller compared to those from goats following S.Japonicum infection for 7 weeks.Besides obvious morphological difference between the schistosomes derived from the two hosts,differences were also observed by scanning and transmission electron microscopy.Microarray analysis revealed 485 differentially expressed genes found in schistosomes between water buffalo and goat.Compared with schistosomes from goats,genes involved in lipid metabolism,genetic information processing,as we11 as protein folding,sorting,and degradation were upregulated in schistosomes from water buffalo,whereas genes associated with signal transduction,endocrine function,development,reproduction,endocytosis,amino acid/carbohydrate metabolism,and immune function,etc.were downregulated.KEGG pathway analysis deduced that the differentially expressed genes mainly involved lipid metabolism,the MAPK and ErbB signaling pathways,progesteronE-mediated oocyte maturation,dorso:ventral axis formation,reproduction,and endocytosis,etc.The microarray gene analysis in schistosomes derived from water buffalo and goats provide a useful platform to disclose differences determining S.japonicum host compatibility to better understand the interplay between natural hosts and parasites,and identify schistosome target genes associated with susceptibility to screen vaccine candidates.