Candidatus Liberibacter solanacearum (CLso) is a regulated plant pathogen in European and some Asian countries, associated with severe disease in economically important Apiaceous and Solanaceous crops, including potato, tomato, carrot and other vegetable plants. Twelve haplotypes of CLso have been identified based on the difference in rRNA, conserved genes, and host specificity. CLso haplotypes A and B are both lethal to potato, causing zebra chip disease in Mexico and USA, whereas some tomato varieties are susceptive to CLso haplotype B, but demonstrated asymptomatic to haplotype A. To date, the virulence mechanisms of the pathogen to the host plants are not clearly illustrated, nor are the plants response or functional decline of the host plants. This study provides insights into plant defense and functional decline of tomato plants to phytopathogenic CLso, using whole transcriptome sequencing with qPCR validation. We sequenced transcriptomes of 27 tomato plants, including six infected by CLso haplotype B, ten infected by CLso haplotype A, and 11 healthy plants using Illumina MiSeq. By comparing haplotype B to A, we found 138 genes were over-expressed, and 331 genes were down-regulated. Besides, the expression levels of healthy and haplotype A infected tomato were alike. Gene set and pathway enrichment shows CLso affected tomato hosts carbohydrate metabolic process, restraining photosynthesis and starch biosynthesis, but promoting starch degradation and assumption. In addition, pathogenic CLso infection suppressed genes in steroid, phenylpropanoid, and flavonoid biosynthesis, hindering plant development, pigmentation, defense and signaling. In conclusion, this study provides insights into plants defense and functional decline due to phytopathogenic CLso. The interactions between host plant and pathogenic CLso provide references for other plants, such as potato plants that face invasion of the same bacteria. Understanding the underlying mechanisms can enhance disease control and create opportunities for breading resistant or tolerant varieties of tomato and potato.