In the 80ies, in Southern Europe and in particular in Ria Formosa there was an episode of heavy mortality of the economically relevant clam Ruditapes (R.) decussatus associated with a debilitating disease (Perkinsosis) caused by Perkinsus olseni. This protozoan parasite was poorly known concerning its’ differential transcriptome in response to its host, R. decussatus. This laboratory available protozoan system was used to identify parasite genes related to host interaction. Beyond the application of molecular biology technologies and methodologies, only the help of Bioinformatics tools allowed to analyze the results of the study. The strategy started with SSH technique, allowing the identification of parasite up-regulated genes in response to its natural host, then a macroarray was constructed and hybridized to characterize the parasite genes expression when exposed to bivalves hemolymph from permissive host (R. decussatus), resistant host (R. philippinarum) and non permissive bivalve (Donax trunculus) that cohabit in the same or adjacent habitats in Southern Portugal. Genes and respective peptides full molecular characterization depended on several Bioinformatic tools application. Also a new Bioinformatic tool was developed.