Neospora caninum is one of the main causes of transmissible abortion in cattle. However, the molecular basis that governs biological variability in N. caninum and the pathogenesis of neosporosis has not been well-established yet. In this study RNA-seq was used to investigate transcriptome differences between the high virulence isolate Nc-Spain7 and the low virulence isolate Nc-Spain1H during tachyzoite egress from host cells (56 hours post-infection). The results showed 550 DEGs between Nc-Spain1H and Nc-Spain7. Among these genes, 369 were over-expressed in Nc-Spain1H and 181 in Nc-Spain-7. A remarkable result was the large number of bradyzoite-specific genes that were over-expressed in the low virulent isolate Nc-Spain1H. This characteristic may

explain, at least partially, its lower virulence since tachyzoite growth (lower in strains that tend to form bradyzoites) is a phenotypic trait related to virulence in N. caninum

and T. gondii. Genes involved in parasite invasion and egress and soluble effectors related to Toxoplasma gondii virulence (ROP and GRA) also showed different expression between isolates. Differential protein abundance analyses by Quantitative label free LC-MS/MS through tachyzoite lytic cycle was also performed. The invasion machinery, metabolism, response to stress and the tendency to form bradyzoites have emerged as principal key factors for isolate behaviour and likely pathogenesis.