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The southern root-knot nematode, Meloidogyne incognita (Kofoid & White) Chitwood,is a major limiting factor in commercial production of cucumber (Cucumis sativus L.) throughout the world.Up to now, there was no cucumber cultivar or breeding line with resistance against M.incognita, which can cause significant yield losses to cucumber worldwide.Recently, an extensive evaluation was performed on a wide range of Cucumis genotypes and a new wild line CmR07 with high resistance to M.incognita was obtained.However, the underlying resistance mechanism remains unclear.In the case, the response of resistant line CmR07 was studied in comparison with susceptible line CmS12 following the nematode infection.Roots of the two Cucumis seedlings were analyzed using histological and biochemical techniques.Transcriptome changes of the resistant reaction were investigated by RNA-seq.The present results showed that penetration and development of the nematode in resistant genotype were reduced when compared to susceptible control.Infection of resistant plant with M.incognita resulted in a hypersensitive reaction.The induction of phenylalanine ammonia lyase and peroxidase activities after infection was greater in resistant roots compared with the susceptible one.Several most relevant genes from the phenylpropanoid biosynthesis, plant hormone signal transduction and plant-pathogen interaction pathway that are involved in resistance to the nematode were significantly altered.Collectively, the resistance in CmR07 to M.incognita is associated with reduced nematode penetration, retardation of nematode development and hypersensitive necrosis.The expression of genes resulting in the deposition of lignin, toxic compounds synthesis, suppression of nematode feeding and resistance protein accumulation, and activation of several transcription factors, all which might contribute to the resistance response to the pest.These results would lead to a better understanding the resistance mechanism and aid in the identification of potential targets resistant to the pest for cucumber genetic improvement.